Despite advances in antibiotic therapy and cardiopulmonary support, septic shock remains a highly lethal disease. Sepsis is the leading cause of death in trauma and immunosuppressed patients hospitalized in intensive care units. Cellular mediators such as the neutrophil may play paradoxical roles in this process. While it is clear that neutropenic patients are at increased risk of developing infection and sepsis, in vitro and in vivo studies suggest that the neutrophil, under the influence of other activated endogenous mediators, has the potential to contribute to tissue injury during sepsis. Colony stimulating factors such as granulocyte (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) are capable of both increasing bone marrow leukocyte production as well as increasing the activity level of circulating and resident tissue cells. Administration of these factors improves survival in irradiated neutropenic animal models and decreases the frequency of infection in neutropenic patients, possibly via both direct bone marrow and peripheral effects. The use of such factors in non-neutropenic patients with sepsis has the potential to be either harmful or beneficial. We have previously developed a canine model of intraperitoneal bacterial sepsis which simulates many of the cardiopulmonary changes occurring during human sepsis. This model has been used in previous studies to define the importance of bacterial virulence factors in the pathogenesis of sepsis and septic shock as well as to study potential modalities of therapy. At the present time we are studying the effects of G-CSF pretreatment in this canine model of intraperitoneal bacterial sepsis. Animals are being pretreated with either low doses of G- CSF, in order to primarily activate peripheral cells, or with high doses of G-CSF, sufficient to not only activate circulating cells but to also increase their number 5 to 10 fold.